Delineating the Roles and Molecular Mechanisms of the Regulated Proteolysis in Ras-Mediated Tumorigenesis and Cancer Metastatsis in Drosophila and in Human Cancer Cells

Leah Colvin Wanshura

Ommatidial Development in Third Instar Larva

Figure A: The Drosophila compound eye provides an excellent model system for investigating the molecular mechanisms underlying cellular communication between major intracellular signaling pathways such as RAS, Notch, Hedgehog and Dpp. The highly ordered and reiterated structure of the Drosophila ommatidia evolves from a sheet of undifferentiated pluripotent epithelial cells called the eye imaginal discs - or the developing eyes (B: T. Wolff and D.F. Ready, Pattern Formation in the Drosophila retina. In: The Development of Drosophila melanogaster, M. Bate & A. Martinez Arias (Eds), Cold Spring Harbor Laboratory Press, 1993). In the developing eyes, this sequence of photoreceptor differentiation occurs with a repeating wave of morphogenetic events that begins in the posterior of the disc and progresses anteriorly. The wave is marked by the passage of the morphogenetic furrow as marked by this Blue marker (dpp). Anterior or ahead of the furrow, cells are unpatterned and dividing, while in and posterior to it, the successive cycles of cell fate induction and differentiation are occurring. The disc has been labeled with an antibody specific to the photoreceptor neurons as shown with the Brown stainings. This system can be used to track the development of photoreceptor neurons and the activation/inactivation of RAS signaling pathway.

Leah attended the University of Minnesota in Minneapolis, MN. She graduated Summa Cum Laude from the University of Minnesota in 2003. Leah worked as an undergraduate laboratory assistant to support herself through 4-years of college. After college, Leah worked as junior scientist and medical technician for two years at the University of Minnesota. Leah entered Mayo Graduate School in 2005 with a strong interest in developmental biology and cancer biology. Leah's thesis project is to delineate the roles and molecular mechanisms of the regulated proteolysis in RAS-mediated tumorigenesis and cancer metastatsis in Drosophila and in human cancer cells. The primary focus of her work is to decipher the signaling events and molecules downstream of RAS that controls cell migratory behavior and cell-cell junction integrity. Ultimately, Leah hopes to find a way to reduce or even eliminate cancer metastatsis in the clinical arena. Leah and her colleagues have shown that epithelial integrity and cell migration can be modulated by RAS-regulated proteolytic pathway. She will take advantage of the well-established and genetically tractable system of Drosophila to begin to identify the molecular mechanisms and key signaling events that control RAS-mediated cell motility, cell movement and metastasis in vivo. Since the signaling pathways that Leah has been working on are highly evolutionarily conserved, Leah hope to apply the knowledge and principles gained from the model organism to help our cancer patients.

Leah is highly creative, artistic, intelligent and independent. Leah loves to create and to teach. She loves to discover nature's hidden treasures and mysteries. Leah is determined to pursue an academic career in the future. She is a perfectionist who likes to climb huge mountains (figuratively and literally). Leah would like to use the bench and her beautiful experiments to express her individuality and creativity.